Association of symptoms of neuropsychological long COVID with imaging and plasma biomarkers

BACKGROUND: Some patients recovered from COVID-19 may experience cognitive and psychological symptoms, such as "brain fog" or neuropsychological long COVID, and its mechanism is unclear. OBJECTIVE: This study aimed to investigate the mechanism of brain damage in neuropsychological long COVID using imaging and blood biomarkers. METHODS: Patients who met the criteria on the "brain fog" screening questionnaire and provided informed consent were enrolled in this study (n = 33; mean age 38.5 years). All participants were examined using magnetic resonance imaging, single-photon emission computed tomography (assessment of regional cerebral blood flow [rCBF]), and blood biomarkers. Neuropsychological tests (Montreal Cognitive Assessment-Japanese version [MoCA-J], Trail Making Test [TMT], Frontal Assessment Battery, Digital Symbol Coding [DSC] test, State-Trait Anxiety Inventory [STAI], and Self-Rating Depression Scale [SDS]) were performed simultaneously. RESULTS: Significant correlations were observed between the MoCA-J score and decreased rCBF in the left occipital lobe and increased rCBF in the right occipital lobe (p < 0.05), between the STAI score and decreased rCBF in the right parietal lobe (p < 0.05), and between the SDS score and decreased rCBF in the right parietal lobe (p < 0.05). The MoCA-J and DSC scores were correlated with plasma levels of neurofilament light chain (p < 0 0.05). The TMT time correlated with plasma glial fibrillary acidic protein levels (p < 0.01). CONCLUSION: This study was a cross-sectional and could not distinguish pathological abnormalities. However, as correlations of neuropsychological long COVID with specific brain regions and plasma biomarkers have been elucidated, conducting a case-control analysis may be worthwhile.